Selective modulation of P-glycoprotein activity by steroidal saponines from Paris polyphylla.
Bio-guided fractionation of the roots of Paris polyphylla (Trilliaceae), based on inhibition of P-glycoprotein-mediated daunorubicin efflux in K562/R7 cell line, led to isolation and identification of the three saponins 3-O-Rha(1-->2)[Ara(1-->4)]Glc-pennogenine, gracillin and polyphyllin D, and the two ecdysteroids 20-hydroxyecdysone and pinnatasterone. These compounds were tested for multidrug reversion on P-glycoprotein (ABCB1) with both drug-selected and transfected cell lines, and also on Breast Cancer Resistance Protein (BCRP/ABCG2). By contrast to a weak efficiency on BCRP, the three saponins displayed significant effects as inhibitors of P-glycoprotein-mediated drug efflux.
Nguyen
Van Thi Bao
VT
Université de Lyon, Laboratoire de Pharmacognosie, UMR 5557 CNRS, Faculté de Pharmacie, 8 avenue Rockefeller, 69373 Lyon Cedex 8, France.
Darbour
Nicole
N
Bayet
Christine
C
Doreau
Agnès
A
Raad
Imad
I
Phung
Binh Hoa
BH
Dumontet
Charles
C
Di Pietro
Attilio
A
Dijoux-Franca
Marie-Geneviève
MG
Guilet
David
D
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors*; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors*; D016572:Cyclosporine / Q000494:pharmacology; D003630:Daunorubicin / Q000378:metabolism*; D004144:Diosgenin / Q000031:analogs & derivatives / Q000302:isolation & purification / Q000494:pharmacology; D018432:Drug Resistance, Multiple / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D026461:Ecdysteroids / Q000302:isolation & purification / Q000494:pharmacology; D004441:Ecdysterone / Q000302:isolation & purification / Q000494:pharmacology; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D020014:K562 Cells; D007938:Leukemia / Q000188:drug therapy / Q000378:metabolism; D019684:Magnoliopsida / Q000737:chemistry; D049990:Membrane Transport Modulators / Q000494:pharmacology; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000037:antagonists & inhibitors*; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D027343:Rhizome; D012503:Saponins / Q000302:isolation & purification / Q000494:pharmacology*; D013150:Spirostans / Q000302:isolation & purification / Q000494:pharmacology; D013256:Steroids / Q000302:isolation & purification / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D016572:Cyclosporine; D003630:Daunorubicin; D004144:Diosgenin; D026461:Ecdysteroids; D004441:Ecdysterone; D007166:Immunosuppressive Agents; D049990:Membrane Transport Modulators; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins; D010936:Plant Extracts; D012503:Saponins; D013150:Spirostans; D013256:Steroids; C539593:3-O-Rha(1-2)(Ara(1-4))Glc-pennogenine; C116614:ABCG2 protein, human; C121203:polyphyllin D; C044934:gracillin